Diffusion Coefficient-Formula Weight (D-FW) Analysis of ²H Diffusion-Ordered NMR Spectroscopy (DOSY)

Abstract

We report extension of the D-FW analysis using referenced (2)H DOSY. This technique was developed in response to limitations due to peak overlay in (1)H DOSY spectra. We find a corresponding linear relationship (R(2) > 0.99) between log D and log FW as the basis of the D-FW analysis. The solution-state structure of THF solvated lithium diisopropyl amide (LDA) in hydrocarbon solvent was chosen to demonstrate the reliability of the methodology. We observe an equilibrium between monosolvated and disolvated dimeric LDA complexes at room temperature. Additionally we demonstrate the application of the (2)H D-FW analysis using a compound with an exchangeable proton that is readily labeled with (2)H. Hence, the (2)H DOSY D-FW analysis is shown to provide results consistent with the (1)H DOSY method, thereby greatly extending the applicability of the D-FW analysis.

Improving the Interpretation of Small Molecule Diffusion Coefficients

“…In order to test SEGWE against a wider range of samples, containing different solvents and solutes, a comprehensive review of the literature for a wide range of diffusion coefficients from a wide range of sources was undertaken. In addition to the original data set in the paper detailing the method, a further 23 papers have been used, ,,− ,,,,− to create a literature data set containing a further 558 measurements of diffusion coefficients of various species in various solvents, spanning a range of molecular weights from 18 to 1273 g mol –1 in 23 different solvents, both deuteriated and protiated. The single biggest source of additional data is that of Crutchfield and Harris, with 200 diffusion coefficients in two solvents at two different temperatures.…”

“…An internal calibration curve based on diffusion measurements of reference compounds within the sample is then produced for each experiment. The method was subsequently extended to include 2 H, 6 Li, and 31 P DOSY experiments. − The internal references used in these studies were chosen for a number of properties including inertness and high solubility, and their chemical shifts were typically far from those of the lithium-containing species studied. These compounds spanned a range of different chemical functionalities including, but not limited to, aromatic compounds, olefins, and TMS.…”

The interpretation of small molecule diffusion coefficients: Quantitative use of diffusion-ordered NMR spectroscopy

“…While a titration experiment monitored by chemical shift will access very similar information, diffusion coefficients are used because they are less sensitive to the presence of impurities than are chemical shifts. LiHMDS was chosen for a preliminary study [189]. It ) and free ( ) ligands (Eq.…”

Hydro/Deutero Deamination of Arylazo Sulfones under Metal- and (Photo)Catalyst-Free Conditions

“…Deuterium-labeled compounds, which are physicochemically nearly identical to the non-deuterated analogues, are widely used in mass spectrometry [1] and in NMR spectroscopy [2], as well as in mechanistic elucidation [3,4,5] and metabolic studies [6,7]. Selectively deuterated compounds in medicine are of crucial importance since deuteration was proved to enhance, in some cases, the metabolic stability of drugs [8].…”